Olefin metathesis converts relatively simple olefinic substrates to complex asymmetric compounds in a clean and efficient manner, and has been shown to eliminate many steps in a synthesis of a target organic molecule. Olefin metathesis is thus of considerable interest in the synthesis of medicinally and biologically significant molecules. With more efficient and selective reactions and catalysts available, therapeutic candidates can be made available to the public more readily and in a more cost effective manner. The main objectives of this program involve the design, synthesis, characterization, and mechanistic exploration of a wide variety of new asymmetric molybdenum- and tungsten-based olefin metathesis catalysts. In addition, these novel chiral catalysts will be used to carry out unique enantioselective C-C bond forming reactions of significant interest to synthetic organic chemists. Particular emphasis will be placed on reactions that lead to the formation of products that cannot be prepared easily through any of the available catalytic or enzymatic routes. Among the reactions of interest will be asymmetric ring-closing, ring-opening, and cross metathesis reactions. In a number of cases the utility of the newly developed reactions will be demonstrated through application to the preparation of biologically significant molecules. The catalysts, methods and concepts that emerge from the proposed studies will allow chemists to access a wider range of molecules of biological interest more efficiently, reliably, and in a highly enantioselective fashion.